Indivior PLC announced FDA approval of the first once-monthly, long-acting injectable (LAI) containing risperidone to treat schizophrenia in adults. Clinically relevant levels were reached after the first injection without use of a loading dose or any supplemental oral risperidone.

The extended-release delivery system forms an S.C. depot that provides sustained levels of risperidone over 1 month. Initial peak risperidone plasma levels occur within 4 to 6 hours of dosing and are due to an initial release of the drug during the depot formation process.

Efficacy of the new formulation was evaluated in a pivotal Phase III randomized, double-blind, placebo-controlled, 8-week study of 354 patients. The study demonstrated an improvement in the primary clinical endpoint, Positive and Negative Syndrome Scale (PANSS) total score at day 57. The improvement in Clinical Global Impression Severity of Illness (CGI-S) was also statistically significant at day 57. Clinical trials were designed for the product to be initiated with neither a loading dose nor any supplemental risperidone.

Safety was evaluated in 814 adults with schizophrenia who received at least one dose during clinical trials. A total of 322 patients were treated with the injectable agent for at least 6 months, with 234 of those treated for at least 12 months. The systemic safety profile was consistent with the known safety profile of oral risperidone.

The most common systemic adverse reactions were increased weight, sedation/somnolence, and musculoskeletal pain. The most common injection-site reactions were injection-site pain and reddening of the skin.

The labeling comes with a boxed warning cautioning that older adult patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death. The agent is not approved for use in patients with dementia-related psychosis.

Astellas Pharma and Pfizer announced FDA approval of enzalutamide for treatment of men with nonmetastatic castration-resistant prostate cancer (CRPC). It is the first and only oral medication FDA approved for both nonmetastatic and metastatic CRPC.

Enzalutamide was first approved by FDA in 2012 to treat patients with metastatic CRPC who had previously received docetaxel, and in 2014, it was granted approval for chemotherapy-naive men with metastatic CRPC.

The updated label is based on results from the Phase III PROSPER trial, which demonstrated that use of enzalutamide plus androgen deprivation therapy (ADT) significantly reduced the risk of developing metastasis or death compared with ADT alone in men with nonmetastatic CRPC.

The most common adverse reactions in the clinical trial were asthenic conditions, hot flush, hypertension, dizziness, nausea, and fall.

Janssen announced FDA approval of darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg under the trade name Symtuza—the first and only complete, darunavir-based single-tablet regimen (STR) for the treatment of HIV-1 in treatment-naive and certain virologically suppressed adults.

Symtuza combines the high barrier to resistance of darunavir with a formulation designed for improved tolerability and the convenience of an STR.

Approval was based on data from two 48-week, noninferiority, pivotal Phase III studies that assessed the safety and efficacy of Symtuza versus a control regimen in adults with no prior antiretroviral history (AMBER) and in virologically suppressed adults (EMERALD).

Results from both trials demonstrated that Symtuza was effective and well tolerated, with up to 95% achieving or maintaining virologic suppression (HIV-1 RNA < 50 c/mL).

The recommended dosage of Symtuza is one tablet taken once daily with food. Symtuza is not recommended in patients with creatinine clearance below 30 mL per minute or those with severe hepatic impairment.

According to the prescribing information, prior to or when initiating treatment with Symtuza, patients should be tested for hepatitis B virus (HBV) infection and renal function, and renal function should be monitored as clinically appropriate during therapy. The agent comes with a boxed warning on the risk of posttreatment acute exacerbation of hepatitis B.

FDA also approved ribociclib in combination with fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine based therapy or following disease progression on endocrine therapy.

This is the first approval that FDA has granted as part of two new pilot programs announced earlier this year that collectively aim to make the development and review of cancer drugs more efficient, while improving FDA’s rigorous standard for evaluating efficacy and safety. With this real-time review, FDA was able to start evaluating the clinical data as soon as the trial results become available, enabling FDA to be ready to approve the new indication upon filing of a formal application with the agency.

Currently the two pilot programs are being used for supplemental applications for already approved cancer drugs and could later be expanded to original drugs and biologics.

Ribociclib was first approved in March 2017 for use with an AI to treat HR-positive, HER2-negative breast cancer in postmenopausal women whose cancer is advanced or has spread to other parts of the body.

FDA approved incobotulinumtoxinA to treat chronic sialorrhea, or excessive drooling, in adult patients. It is the first and only neurotoxin with this approved indication in the United States.

Sialorrhea is a common symptom among patients who have neurological disorders such as Parkinson disease, amyotrophic lateral sclerosis, or cerebral palsy or who have had a stroke. The condition can occur from difficulty retaining saliva inside the mouth, from issues with swallowing, and from problems controlling facial muscles.

Approval for this indication was based on a Phase III, randomized, double-blind, placebo-controlled, multicenter trial involving 184 patients in which both coprimary endpoints were successfully achieved. Study participants received placebo (n = 36), incobotulinumtoxinA 75 U (n = 74), or incobotulinumtoxinA 100 U (n = 74). Overall frequency of adverse events was similar between placebo and treatment groups, with no new or unexpected adverse events reported.

This is the fourth neurological indication for the neurotoxin, which was first approved by FDA in 2010 to treat cervical dystonia and blepharospasm (in patients previously treated with onabotulinumtoxinA) in adult patients and later in 2015 for upper limb spasticity in adult patients.

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